PCT WO 84/001106, filed 23 Sep. 1983, describes transforming growth factor .beta.1 (TGF-.beta.1) and its use for the promotion of cell proliferation and tissue repair, wound healing, and treatment of traumata.
U.S. Pat. No. 4,848,063 describes two cartilage inducing factors, CIF-A and CIF-B, found in mammalian bone that (1) are cofactors for inducing cartilage formation in vivo; (2) promote connective tissue deposition in vivo in the absence of any added activating agent or cofactor, and (3) are active in the anchorage-independent cell growth assay used to characterize TGF-.beta. (this assay is sometimes called the TGF-.beta. assay herein and is described in Methods for Preparation of Media, Supplements, and Substrate for Serum-free Animal Cell Culture (1984) pp. 181-194, Alan R. Liss, Inc.).
U.S. Pat. No. 4,806,523, filed 6 Mar. 1986, discloses that CIF-A and CIF-B both possess anti-inflammatory activity and are inhibitors of mitogen stimulated T cell proliferation and B cell activation. It also reports that CIF is localized in centers of hematopoiesis and lymphopoiesis and that CIF may, therefore, be useful for treating indications associated with malfunction or dysfunction of hematopoiesis or lymphopoiesis. CIF-A has since been shown to be identical to TGF-.beta.1. CIF-B has since been recognized as a new form of .beta.-type transforming growth factor and is now called TGF-.beta.2.
U.S. Pat. No. 4,886,747 discloses a third .beta.-type transforming growth factor called TGF-.beta.3.
TGF-.beta.1, TGF-.beta.2, and TGF-.beta.3 are all composed of two identical polypeptide chains linked by disulfide bonds, i.e., they are homodimers. The heterodimer of TGF-.beta.1 and TGF-.beta.2, called TGF-.beta.1.2, has been identified and its uses demonstrated. PCT WO 88/05788, filed 29 Jan. 1988, discloses a heterodimer of TGF-.beta.1 and TGF-.beta.2. PCT WO 90/00900, filed 20 Jul. 1989, discloses treatment of inflammatory disorders with homodimeric TGF-.beta.1 and 2, and the heterodimer TGF-.beta.1.2.